Ethanol protects from injury due to ischemia and reperfusion by increasing vascularity via vascular endothelial growth factor

• Published in: Alcohol (Fayetteville, N.Y.) Vol. 46; no. 5; pp. 441 - 454
• Main Authors: Louboutin, Jean-Pierre, Marusich, Elena, Gao, Ehre, Agrawal, Lokesh, Koch, Walter J, Strayer, David S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2012; Elsevier Limited
• Subjects: Angiogenesis; Animals; Antibodies, Monoclonal, Humanized - pharmacology; Bevacizumab; Brain - blood supply; Capillaries - growth & development; Coronary Vessels - physiology; Diet; Ethanol; Ethanol - administration & dosage; Ethanol - therapeutic use; Male; Muscle, Skeletal - blood supply; Muscle, Skeletal - physiology; Myocardial ischemia/reperfusion; Myocardial Reperfusion Injury - prevention & control; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Post-ischemic neovascularization; Proteins; Psychiatry; Rats; Rats, Sprague-Dawley; Regeneration - physiology; Rodents; Skeletal muscle regeneration; Up-Regulation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis; VEGF; Skeletal muscle regeneration; Angiogenesis; Myocardial ischemia/reperfusion; Ethanol; VEGF; Post-ischemic neovascularization
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2012.02.001

Abstract The cardioprotective effects of moderate ethanol consumption have been known for years and have generally been ascribed to long-term effects of alcohol on blood lipids. However, other mechanisms, particularly ethanol-induced increase in blood vessel density, may also be involved. Our goal was to understand the relationship between ethanol consumption, new blood vessel formation in vivo and protection from injury due to ischemia and ischemia/reperfusion. Using paired ethanol fed and control rats, we assessed capillary density in the heart, brain and skeletal muscle by immunostaining and quantified expression of vascular endothelial growth factor (VEGF) by Western blot analysis and immunocytochemistry. Numbers of vessels were significantly increased in the brain, heart and skeletal muscle of animals fed ethanol-rich diets. VEGF (and its receptors) were upregulated in these organs. These effects were very rapid: highly significantly increased vascularization was seen within 2 weeks of commencing alcohol feeding. A neutralizing VEGF antibody, bevacizumab, inhibited new blood vessel formation induced by moderate doses of ethanol. Ethanol consumption increased vascularization and promoted skeletal muscle regeneration following hindlimb ischemia; these effects were prevented by bevacizumab. Finally, ethanol consumption protected myocardium following experimental ischemia/reperfusion. Conclusion: Experimental ethanol ingestion rapidly increases VEGF production, significantly increasing the capillary bed in the heart, brain, and skeletal muscle. Moreover, the ethanol-induced increase of blood vessel density is protective against ischemic events (i.e., hindlimb ischemia and myocardium ischemia/reperfusion) and promotes skeletal muscle regeneration.